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1.
Immunotargeting of daunomycin to localized and metastatic human colon adenocarcinoma in athymic mice
Esther Hurwitz Ruth Adler Daniel Shouval Hiroshi Takahashi Jack R. Wands Michael Sela 《Cancer immunology, immunotherapy : CII》1992,35(3):186-192
Summary A monoclonal antibody (designated SF25), which recognizes a protein antigen expressed on a large number of human colon carcinomas, was used for drug targeting. Daunomycin-antibody conjugates were prepared by two previously described procedures. In one, the drug was bound to the antibody through a spacer of small molecular mass (cis-aconitic acid), while in the other a dextran bridge served as the link between drug and antibody. High substitution rates of drug to antibody were obtained using the latter binding procedure. Both conjugates were tested in vitro against two human colon carcinoma cell lines, LS180 and KM-12. The efficacy of a daunomycin-dextran-SF25 antibody conjugate was tested against colon carcinoma LS180 tumors transplanted at different sites into athymic mice. The specific conjugate was significantly more inhibitory to a subcutaneous tumor growth than its components or their mixture. SF25 antibody alone showed antitumoral effects against all three forms of transplanted tumor tested, namely, local, metastatic or intrahepatic, whereas daunomycin, on its own, was effective only against the subcutaneous tumor. Binding of daunomycin to dextran partially improved its inhibitory activity against the metastatic tumor. The conjugate, daunomycin-dextran-SF25 antibody reduced the number of metastatic foci, increased the survival rate and delayed death. Yet against lymph node metastases it was not significantly better than a mixture of both constituents. However, results obtained with an intrahepatic tumor, a model that mimics the natural progression of the disease, resembled those described with the subcutaneous tumor. Daunomycin-dextran-SF25 antibody was significantly more effective than all components separately and than a mixture of drug and antibody, provided a highly drug-substituted conjugate was used. 相似文献
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The phylogeny of Greya Busck (Lepidoptera: Prodoxidae) was inferred from
nucleotide sequence variation across a 765-bp region in the cytochrome
oxidase I and II genes of the mitochondrial genome. Most parsimonious
relationships of 25 haplotypes from 16 Greya species and two outgroup
genera (Tetragma and Prodoxus) showed substantial congruence with the
species relationships indicated by morphological variation. Differences
between mitochondrial and morphological trees were found primarily in the
positions of two species, G. variabilis and G. pectinifera, and in the
branching order of the three major species groups in the genus. Conflicts
between the data sets were examined by comparing levels of homoplasy in
characters supporting alternative hypotheses. The phylogeny of Greya
species suggests that host-plant association at the family level and larval
feeding mode are conservative characters. Transition/transversion ratios
estimated by reconstruction of nucleotide substitutions on the phylogeny
had a range of 2.0-9.3, when different subsets of the phylogeny were used.
The decline of this ratio with the increase in maximum sequence divergence
among taxa indicates that transitions are masked by transversions along
deeper internodes or long branches of the phylogeny. Among transitions,
substitutions of A-->G and T-->C outnumbered their reciprocal
substitutions by 2-6 times, presumably because of the approximately 4:1
(77%) A+T-bias in nucleotide base composition. Of all transversions,
73%-80% were A<-->T substitutions, 85% of which occurred at third
positions of codons; these estimates did not decrease with an increase in
maximum sequence divergence of taxa included in the analysis. The high
frequency of A<-->T substitutions is either a reflection or an
explanation of the 92% A+T bias at third codon positions.
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Lun He Kurt J. Isselbacher Jack R. Wands Howard M. Goodman Chiaho Shih Andrea Quaroni 《In vitro cellular & developmental biology. Plant》1984,20(6):493-504
Summary A human hepatocellular carcinoma cell line (FOCUS—Friendship of China and United States) was derived from a patient with primary
hepatocellular carcinoma. This cell line has been in continuous culture over an 18-mo period. The morphological and ultrastructural
features of FOCUS are consistent with its neoplastic hepatocellular orgin. FOCUS cells contain aspartate aminotransferase
and glucose-6-phosphatase activity. In addition, α1-antitrypsin, fibrinogen, alpha fetoprotein, and carcinoembryonic antigens were detectble in the cytoplasm of the cultured
cells by immunochemical staining techniques. The karyotype of the FOCUS cell is human in origin and it contains human DNA
sequences as detected by molecular hybridization analysis. The FOCUS cells do not show evidence of density-dependent inhibition
of growth under confluent conditions. Repeated growth curves over an 18-mo period were identical, revealing a doubling time
of 42 to 48 h. The malignant potential of FOCUS cells was further demonstrated by their ability to lead to gross tumor formation
after subcutaneous infection into nude mice. From one of the solid tumors grown in nude mice, recultured cell lines have been
established and found to have properties identical to the original FOCUS cell line. This FOCUS cell line represents an additional
model for further investigation of tumor specific antigens and the relationship between hepatitis B virus (HBV) and hepatocellular
carcinoma. Preliminary molecular characterization has indicated the existence of integrated HBV sequences within the FOCUS
genome. 相似文献
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